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    LPA lipoprotein(a) [ Homo sapiens (human) ]

    Gene ID: 4018, updated on 27-Dec-2024

    Summary

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    Official Symbol
    LPAprovided by HGNC
    Official Full Name
    lipoprotein(a)provided by HGNC
    Primary source
    HGNC:HGNC:6667
    See related
    Ensembl:ENSG00000198670 MIM:152200; AllianceGenome:HGNC:6667
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    LP; AK38; APOA
    Summary
    The protein encoded by this gene is a serine proteinase that inhibits the activity of tissue-type plasminogen activator I. The encoded protein constitutes a substantial portion of lipoprotein(a) and is proteolytically cleaved, resulting in fragments that attach to atherosclerotic lesions and promote thrombogenesis. Elevated plasma levels of this protein are linked to atherosclerosis. Depending on the individual, the encoded protein contains 2-43 copies of kringle-type domains. The allele represented here contains 15 copies of the kringle-type repeats and corresponds to that found in the reference genome sequence. [provided by RefSeq, Dec 2009]
    Expression
    Restricted expression toward liver (RPKM 48.1) See more
    Orthologs
    all
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    Genomic context

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    See LPA in Genome Data Viewer
    Location:
    6q25.3-q26
    Exon count:
    39
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (160531482..160664275, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (161783172..162011762, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (160952514..161085307, complement)

    Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC124901453 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:160807441-160807942 Neighboring gene solute carrier family 22 member 3 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25402 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr6:160907332-160908531 Neighboring gene lipoprotein(a) like 2 (pseudogene) Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17759 Neighboring gene uncharacterized LOC124901454 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17760 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17761 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr6:161025992-161027191 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:161106525-161107079 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17762 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr6:161158745-161159944 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25403 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17763 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17764 Neighboring gene plasminogen Neighboring gene plasminogen-like protein B Neighboring gene NANOG hESC enhancer GRCh37_chr6:161200290-161200791 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25404 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25405 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25406 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_91154 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr6:161262159-161263358 Neighboring gene uncharacterized LOC112267969 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:161298543-161299475 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:161303800-161304432 Neighboring gene MPRA-validated peak6293 silencer Neighboring gene MPRA-validated peak6294 silencer Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr6:161309865-161310670 Neighboring gene MPRA-validated peak6295 silencer

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: Tissue-specific circular RNA induction during human fetal development
    • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
    • BioProject: PRJNA270632
    • Publication: PMID 26076956
    • Analysis date: Mon Apr 2 22:54:59 2018

    Bibliography

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    Related articles in PubMed

    1. Lack of association between lipoprotein(a) genetic variants and subsequent cardiovascular events in Chinese Han patients with coronary artery disease after percutaneous coronary intervention. Li ZG, et al. Lipids Health Dis, 2013 Aug 27. PMID 23978127, Free PMC Article
    2. HIV disease activity as a modulator of lipoprotein(a) and allele-specific apolipoprotein(a) levels. Enkhmaa B, et al. Arterioscler Thromb Vasc Biol, 2013 Feb. PMID 23202367, Free PMC Article
    3. Effect of specific lipoprotein(a) apheresis on coronary atherosclerosis regression assessed by quantitative coronary angiography. Safarova MS, et al. Atheroscler Suppl, 2013 Jan. PMID 23357149
    4. Extreme lipoprotein(a) levels and improved cardiovascular risk prediction. Kamstrup PR, et al. J Am Coll Cardiol, 2013 Mar 19. PMID 23375930
    5. Genetic associations with valvular calcification and aortic stenosis. Thanassoulis G, et al. N Engl J Med, 2013 Feb 7. PMID 23388002, Free PMC Article

    See all (513) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Lipoprotein (a) as a Cardiovascular Risk Factor in Controversial Clinical Scenarios: A Narrative Review.
      Title: Lipoprotein (a) as a Cardiovascular Risk Factor in Controversial Clinical Scenarios: A Narrative Review.
    2. Identification of allele-specific KIV-2 repeats and impact on Lp(a) measurements for cardiovascular disease risk.
      Title: Identification of allele-specific KIV-2 repeats and impact on Lp(a) measurements for cardiovascular disease risk.
    3. Lipoprotein(a) and Long-Term Plaque Progression, Low-Density Plaque, and Pericoronary Inflammation.
      Title: Lipoprotein(a) and Long-Term Plaque Progression, Low-Density Plaque, and Pericoronary Inflammation.
    4. Lipoprotein(a) levels and carotid intima-media thickness in children: A 20-year follow-up study.
      Title: Lipoprotein(a) levels and carotid intima-media thickness in children: A 20-year follow-up study.
    5. Confounding Factors Responsible for Elevated Lp(a) Levels in Patients with Coronary Artery Disease.
      Title: Confounding Factors Responsible for Elevated Lp(a) Levels in Patients with Coronary Artery Disease.
    6. Association of Lipoprotein(a) with arterial stiffness: A Mendelian randomization study.
      Title: Association of Lipoprotein(a) with arterial stiffness: A Mendelian randomization study.
    7. Lipoprotein(a), platelet function and cardiovascular disease.
      Title: Lipoprotein(a), platelet function and cardiovascular disease.
    8. Lipoprotein(a) is associated with recurrent cardiovascular events in patients with coronary artery disease and prediabetes or diabetes.
      Title: Lipoprotein(a) is associated with recurrent cardiovascular events in patients with coronary artery disease and prediabetes or diabetes.
    9. Association between lipoprotein (a) and risk of heart failure: A systematic review and meta-analysis of Mendelian randomization studies.
      Title: Association between lipoprotein (a) and risk of heart failure: A systematic review and meta-analysis of Mendelian randomization studies.
    10. Diacylglycerols and Lysophosphatidic Acid, Enriched on Lipoprotein(a), Contribute to Monocyte Inflammation.
      Title: Diacylglycerols and Lysophosphatidic Acid, Enriched on Lipoprotein(a), Contribute to Monocyte Inflammation.
    Submit: New GeneRIF Correction See all GeneRIFs (444)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    LIPOPROTEIN(a) QUANTITATIVE TRAIT LOCUS
    MedGen: C5394134 OMIM: 618807 GeneReviews: Not available
    		Compare labs

    EBI GWAS Catalog

    Description
    A genome-wide association study identifies protein quantitative trait loci (pQTLs).
    EBI GWAS Catalog
    Biological, clinical and population relevance of 95 loci for blood lipids.
    EBI GWAS Catalog
    Discovery and refinement of loci associated with lipid levels.
    EBI GWAS Catalog
    Genetic and clinical correlates of early-outgrowth colony-forming units.
    EBI GWAS Catalog
    Genetic associations with valvular calcification and aortic stenosis.
    EBI GWAS Catalog
    Genetic determinants of statin-induced low-density lipoprotein cholesterol reduction: the Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial.
    EBI GWAS Catalog
    Genetic variants in PLG, LPA and SIGLEC 14 as well as smoking contribute to plasma plasminogen levels.
    EBI GWAS Catalog
    Genetic variants, plasma lipoprotein(a) levels, and risk of cardiovascular morbidity and mortality among two prospective cohorts of type 2 diabetes.
    EBI GWAS Catalog
    Genome-wide association study evaluating lipoprotein-associated phospholipase A2 mass and activity at baseline and after rosuvastatin therapy.
    EBI GWAS Catalog
    Genome-wide association study of genetic determinants of LDL-c response to atorvastatin therapy: importance of Lp(a).
    EBI GWAS Catalog
    Genome-wide association study of plasma lipoprotein(a) levels identifies multiple genes on chromosome 6q.
    EBI GWAS Catalog
    Genome-wide characterization of shared and distinct genetic components that influence blood lipid levels in ethnically diverse human populations.
    EBI GWAS Catalog
    Genome-wide haplotype association study identifies the SLC22A3-LPAL2-LPA gene cluster as a risk locus for coronary artery disease.
    EBI GWAS Catalog
    Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease.
    EBI GWAS Catalog
    Novel association to the proprotein convertase PCSK7 gene locus revealed by analysing soluble transferrin receptor (sTfR) levels.
    EBI GWAS Catalog
    Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins.
    EBI GWAS Catalog
    Shared genetic susceptibility to ischemic stroke and coronary artery disease: a genome-wide analysis of common variants.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables apolipoprotein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables endopeptidase inhibitor activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables fibronectin binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables heparin binding NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables serine-type endopeptidase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in blood circulation TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in lipid metabolic process NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in lipid transport IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in extracellular region NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    located_in extracellular region TAS
    Traceable Author Statement
    more info
    		  
    part_of plasma lipoprotein particle IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    apolipoprotein(a)
    Names
    antiangiogenic AK38 protein
    apo(a)
    lipoprotein, Lp(a)
    lp(a)
    NP_005568.2

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_016147.1 RefSeqGene

      Range
      7101..139894
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_005577.4 → NP_005568.2  apolipoprotein(a) precursor

      See identical proteins and their annotated locations for NP_005568.2

      Status: REVIEWED

      Source sequence(s)
      AL109933, AL596089
      Consensus CDS
      CCDS43523.1
      UniProtKB/Swiss-Prot
      P08519, Q5VTD7, Q9UD88
      UniProtKB/TrEMBL
      Q1HP67
      Related
      ENSP00000321334.6, ENST00000316300.10
      Conserved Domains (4) summary
      smart00020
      Location:1820 → 2033
      Tryp_SPc; Trypsin-like serine protease
      smart00130
      Location:1614 → 1695
      KR; Kringle domain
      cd00190
      Location:1820 → 2034
      Tryp_SPc; Trypsin-like serine protease; Many of these are synthesized as inactive precursor zymogens that are cleaved during limited proteolysis to generate their active forms. Alignment contains also inactive enzymes that have substitutions of the catalytic triad ...
      pfam00051
      Location:28 → 105
      Kringle; Kringle domain

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000006.12 Reference GRCh38.p14 Primary Assembly

      Range
      160531482..160664275 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060930.1 Alternate T2T-CHM13v2.0

      Range
      161783172..162011762 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P08519.2 GenPept UniProtKB/Swiss-Prot:P08519

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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